Premenstrual Syndrome

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This is a condition which manifests with "distressing physical, behavioural and psychological symptoms, in the absence of organic or underlying psychiatric disease, which regularly recurs during the luteal phase of each menstrual (ovarian) cycle and which disappears or significantly regresses by the end of menstruation".[1]The key characteristic is the timing of the symptoms; by definition, there will be a clear symptom-free interval at some time between the end of menstruation and the estimated time of ovulation.[2]

PMS is distinguished from normal psychological and physical symptoms experienced by the majority of women premenstrually, by the severity of the distress they cause and the negative effect they have on daily life. Severe PMS is referred to as premenstrual dysphoric disorder (PMDD) and PMD encompasses both PMS and PMDD.

It has been proposed that PMD be classified into 'Core PMD' and 'Variants of PMD', such as significant premenstrual exacerbation of an underlying disorder or symptoms due to exogenous progestogen administration - for example, that found in hormone replacement therapy (HRT).[2]

Aetiology

As symptoms come and go in line with the menstrual cycle, it has long been thought that sex steroid hormonal changes were responsible for PMS. To fit with this theory, symptoms tend to be absent during non-ovulatory cycles, abolished by oophorectomy or treatment with ovulation inhibitors, and return with administration of exogenous hormones.[3]However, the mechanism by which the changing hormone levels cause PMS symptoms is still elusive.

An alternative theory involves sex steroids and their effect on serotonin within the brain. Animal modelling has shown that serotonin may have a role modifying the effects of sex steroid-driven behaviour such as aggression and mood. In this theory, serotonin deficiency would create excessive swings in those behaviours. Also within this model, somatic symptoms such as breast tenderness and bloating represent a lack of willingness to tolerate these (normal) changes whilst being in a dysphoric state.

It has been suggested that PMS may confer an evolutionary advantage by increasing the chances of an infertile couple breaking up, thus improving the reproductive chances of the woman in such partnerships.[4].

Epidemiology

Between 5-8% of women fulfil the criteria for a diagnosis of PMS; about 20% of these women seek medical help.[3]

Risk factors

Presentation

Symptoms vary between cycles; they tend to worsen markedly about six days prior to menses and peak at two days beforehand and there is always a symptom-free time in the cycle, usually after starting the period. The main symptoms leading to a consultation are irritability and inability to cope with domestic or workplace demands.

Physical symptoms usually lead to a consultation only when mastalgia, dysmenorrhoea or migraine have not responded to self-management.

Difficult interpersonal relationships with a spouse or children may also precipitate a consultation. The risk of perimenopausal and postnatal depression as well as anxiety disorders, appears to be higher amongst women with PMD.[3]

Psychosexual problems, loss of libido and dyspareunia may be reported but usually have to be specifically asked about.

There are no specific signs of the syndrome, so the problem is best delineated on the basis of a history and symptom diary kept over 2-3 months. There may be leg or breast oedema.

The clinician should be particularly careful not to accept without question parent-reported diagnosis of PMS in adolescent girls who may have more serious underlying psychological illness.

Differential diagnosis

The clinician should be careful to make a proper assessment before attributing symptoms to PMS, to avoid missing other causes of erratic or dysphoric behaviour.

Investigations

Ask the patient to keep a symptom diary over two complete cycles, to help with diagnosis. An online facility for doing this is provided by Symptometrics. Later this will also help to assess effectiveness of any interventions.

Check blood pressure and pulse rate.

Consider breast and thyroid examination, as appropriate.

Consider pelvic examination, particularly if bloating is a major problem (this may be ascites due to alternative ovarian pathology), or other reason to suspect a physical cause of abdominal swelling.

There are no useful tests to confirm the diagnosis. Consider other blood tests only if there is reason to suspect an alternative physical cause for symptoms.

Management

General measures

The most important part of the management is to reassure the patient that you understand her concerns and the disruption that symptoms are causing to her life. Quite often the friction caused by her irritability and volatility alienates the patient from usual sources of support at work and home. As PMS can be a long-term problem, there are lifestyle changes that may help the patient to cope with the symptoms. Reassure her that there are many ways to help and it is a matter of finding the best treatment strategy. Mild symptoms may respond to lifestyle changes:[6]

Reducing saturated fats and caffeine: may improve mastalgia. Good diet may correct any subclinical nutrient deficiencies (eg, magnesium and calcium) and improve symptoms.

Reducing salt intake: may reduce fluid retention.

Use of a firm, supportive bra - day and night.

Support stockings: to help aching legs.

Exercise is effective in some women.

Try rescheduling more stressful tasks to the better half of the month and keep a note of when the next cycle is due so as to be prepared. Suggest to the patient that she explains PMS to friends and family to improve support. Cognitive behavioural therapy (CBT) may be useful in motivated patients and in one study comparing CBT with fluoxetine, CBT was superior in long-term efficacy although not as good for anxiety.[7]Relaxation exercises are helpful, as are methods of coping with stress, such as assertiveness and time management training; any strategy that reduces overall stress is likely to improve PMS to a degree. Other remedies such as fennel tea and camomile tea may reduce breast tenderness; they act as a good substitute for tea and coffee, which may aggravate irritability further.

Many dietary supplements and herbal remedies have been proposed to aid PMS. The strongest evidence for the effectiveness of other non-drug treatments is for calcium supplements, chasteberry (vitex agnus castus) and CBT.[7]Vitamin B6 is suggested as a first-line treatment option by the Royal College of Obstetricans and Gynaecologists, but results from research are mixed.

Pharmacological

Many treatments have been put forward but few have supportive evidence to justify their use. Treatment needs to be tailored to the severity of the PMS. Try simple analgesia, as required, for breast tenderness, headaches and period pains. Pharmacological options fall into two broad categories: those that affect brain neurotransmitters, particularly serotonin, and those that interfere with ovulation.[7]

Psychotropics - selective serotonin reuptake inhibitors (SSRIs):

SSRIs are first-line for women over 18 years of age with severe PMS. They have been shown to be effective in many trials, with 60-90% of women showing improvement with active treatment versus 30-40% for placebo treatments.[8]

SSRIs reduce both mood symptoms and somatic complaints and can be prescribed in primary care for women who predominantly have mood symptoms. This is an off-label use and the woman should be told this.

The short onset of action enables limiting their use to the symptomatic luteal phase of the menstrual cycle, typically starting 14 days before menstruation is expected and continuing until bleeding starts.

They may be effective taken 'as required' but there is currently limited evidence for this strategy.[7]

Suppression of ovulation

Combined hormonal contraceptives (CHCs) are commonly thought to improve symptoms but there are few good trial data to support their use. Drospirenone plus 20 mg estradiol may help reduce PMS symptoms but a Cochrane review concluded that any superiority over other CHCs was unclear.[9]Taking a CHC continuously for three cycles may reduce PMS symptoms and may be an option for women who want to use CHCs for contraception.[10]

Transdermal oestrogen is one of the more effective treatments for PMS symptoms. It should be given as a transdermal patch, gel or subcutaneous implant, as oral oestrogen is usually insufficient to suppress ovulation; 100, 150, or 200 micrograms may be necessary. Due to the unknown effects of these preparations on the risk of endometrial or breast cancer, the National Institute for Health and Care Excellence (NICE) does not recommend their use in primary care.[6]If the woman has an intact uterus she will need to be given a progestogen to prevent endometrial hyperplasia. A levonorgestrel-containing intrauterine system (IUS-LNG) delivers this without causing symptoms to return.[1]

Use of gonadotrophin-releasing hormone (GnRH) analogues with HRT add-back therapy achieves ovulation inhibition whilst also providing uterine protection. No particular form of HRT appears to be better than any other. Response rate is reported to be between 60-75%.[7]Women having long-term ovulation inhibition (> 6 months) should have annual DEXA scans whilst on treatment.

Danazol, although effective in reducing premenstrual breast pain, is rarely used now due to the risk of masculinisation and other side-effects.[7]

Progestogen alone is not recommended for women with PMS, due to insufficient evidence to support its effectiveness.[11]

The IUS-LNG alone may be effective and is not contra-indicated in women with PMS requesting an intrauterine device for contraception. In a randomised trial to compare LNG-IUS and hysterectomy in the treatment of heavy menstrual bleeding over a ten-year period, secondary analysis of a five-year period demonstrated an improvement in premenstrual symptoms in both groups.[12]

Surgery

There is no evidence supporting routine use of surgical treatments for PMS. Hysterectomy that must include oophorectomy, with oestrogen-only HRT, should be a last resort for the treatment of severe PMD and the risk versus benefit ratio should be carefully considered and documented. If a severe sufferer is certain that she does not want any more children, then it may be an option to consider.

Complications

PMS has been considered as a mitigating circumstance in some courts, for certain minor criminal offences such as shoplifting. Notoriously in two murder case in England in 1979, proof that PMS resulted in uncontrollable behaviour was used by the defence, resulting in a reduction in charges against the accused.[13]

Prognosis

Most women can find effective solutions to their symptoms. A small number of women continue to be affected severely with worsening symptoms until the menopause.

Article Information

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